The development of a bacterial biofilm is fundamental to the progression of periodontal disease. Porphyromonas gingivalis is an opportunistic pathogen that resides within the subgingival crevice of the oral cavity. This Gram-negative anaerobe is a causative agent of severe and chronic cases of periodontal disease, a condition characterized by destruction of the tissue supporting the gums, and ultimately, tooth loss. In our preliminary studies, we identified a previously uncharacterized region of the chromosome involved in the synthesis of capsule. Through mutational analysis we determined that capsule expression blocks biofilm development, while a lack of capsule expression enhances biofilm formation. Our long-term goal is to fully characterize this predicted operon at the molecular level and to elucidate how capsule synthesis and the coordinate expression of other surface structures relates to the switch from an in-biofilm life-style to a planktonic virulent state. The objective of this application is to identify nutritional and environmental parameters that control the expression of this locus, including in-biofilm expression studies. The research proposed in this application is significant because understanding the control of capsule expression is a vital link to understanding the switch this bacterium makes from a commensal organism persisting in a biofilm to a virulent pathogen. As an outcome of these studies, we will have established the expression profile of genes involved in capsule synthesis and determined the relationship between capsule expression and biofilm growth. This information will lead to a better understanding of signals that either direct P. gingivalis to become a virulent pathogen or to continue to lie low and persist. Our results will potentially lead to the development of new therapeutic strategies for modulating biofilm formation by this oral pathogen. [unreadable] [unreadable] [unreadable]